Programmed Death Ligand-1 (PD-L1) is a surface glycoprotein ligand for PD-1, a key immune checkpoint receptor expressed by activated T and B cells and mediates immunosuppression, which is found on both antigen-presenting cells and human cancers and downregulaes T cell activation and cytokine secretion by binding to PD-1 (Freeman et al., 2000; Latchman et al, 2001). Inhibition of the PD-L/PD-1 interaction allows for potent anti-tumor activity in preclinical models, and antibodies that disrupt this interaction have entered clinical trials for the treatment of cancer (U.S. Pat. Nos. 8,008,449 and 7,943,743; Brahmer et al., 2010; Topalian et al., 2012b; Brahmer et al., 2012; Flies et al., 2011; Pardoll, 2012; Hamid and Carvajal, 2013).
PET, or Positron Emission Tomography, is a non-invasive, nuclear medicine technique that produces a three-dimensional image of various molecular processes within the body, or the location of proteins associated with disease pathology. The methodology detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer) introduced into the body on a biologically active molecule. PET imaging tools have a wide variety of uses for drug development and have a unique translational medicine advantage, in that the same tool could be used both preclinically and clinically. Examples include direct visualization of in vivo saturation of targets; monitoring uptake in normal tissues to anticipate toxicity or patient to patient variation; quantifying diseased tissue; tumor metastasis; monitoring drug efficacy over time, or resistance over time, and more.
Described herein are novel anti-PD-L1 Adnectins suitable for use as diagnostic/imaging agents, for example, for use in positron emission tomography.